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Combining Anti-PD-L1 Immune Checkpoint Inhibitor Durvalumab With TLR-3 Agonist Rintatolimod in Patients With Metastatic Pancreatic Ductal Adenocarcinoma for Therapy Efficacy

NCT05927142 · Status: RECRUITING · Phase: PHASE1/PHASE2 · Type: INTERVENTIONAL · Enrollment: 43

Last updated 2025-02-25

No results posted yet for this study

Summary

Pancreatic ductal adenocarcinoma (PDAC) is estimated to become the second leading cause of cancer-related death by 2030. Effective management of PDAC is challenged by a combination of late diagnosis, lack of effective screening methods and high risk of early metastasis. Although systemic chemotherapy improves survival, 5-year survival is only 6%. Chemotherapy efficacy is attenuated by innate and acquired drug resistance of tumor cells, a strong desmoplastic reaction that limits local accessibility of drugs and a "cold" tumor microenvironment (TME) with high infiltrating levels of immunosuppressive cells. In PDAC, increased T cell exhaustion defined by increased PD-1/PD-L1 activity in both peripheral blood and tumor microenvironment, is associated with poor prognosis. Hence the rationale for targeting the PD-1/PD-L1 axis with the aim to release the "brake" and exert an anti-tumor response. In PDAC successful results with Immune Checkpoint Inhibition (ICI) monotherapy are limited and combination therapy with other agents is encouraged; specifically agents that induce dendritic cell priming. We hypothesize that combination therapy of ICI therapy with a toll like receptor 3 (TLR-3) agonist is a potential effective strategy. TLR-3 agonists are hypothesized to increase dendritic cell maturation and cross-priming naïve cytotoxic CD8 T cells while eliminating regulatory T-cell attraction, thereby acting as an immune-boosting agent. We propose that rintatolimod/durvalumab-combination therapy is feasible and may induce synergistic anti-tumor immune responses in PDAC.

Conditions

Interventions

BIOLOGICAL

Durvalumab

Human anti-PD-L1 antibody

DRUG

Rintatolimod

TLR-3 agonist, synthetic double-stranded ribonucleic acid (poly I:C12U)

Sponsors & Collaborators

Principal Investigators

  • Marjolein Homs, PhD · Erasmus Medical Center

  • Casper van Eijck, Prof, MD, PhD · Erasmus Medical Center

  • Songul Kucukcelebi, MD · Erasmus Medical Center

Study Design

Allocation
NA
Purpose
OTHER
Masking
NONE
Model
SEQUENTIAL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2024-01-09
Primary Completion
2026-04-30
Completion
2027-04-30

Countries

  • Netherlands

Study Locations

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Entities

Drugs
Diseases
Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05927142 on ClinicalTrials.gov